磷酸奥司他韦对上海及周边地区不同流行性感冒病毒亚型的体外抗病毒效果

The study on in vitro biological effect of oseltamivir carboxylate against various subtype of influenza virus from Shanghai and its surrounding places

目的了解上海及周边地区近年来流行性感冒（流感）病毒流行株对磷酸奥司他韦的敏感度及是否存在耐药株。方法从2004-2006年上海市、江苏省无锡市和浙江省德清县流感监测和暴发病例分离到的流感病毒中，随机抽取B型、H1亚型、H3亚型的部分流感病毒，用中性红吸收法在体外检测磷酸奥司他韦的抗病毒作用，以50％抑制浓度（IC50）表示药物的抗病毒效果。方差分析检验药物对各亚型流感株IC50的差异。结果磷酸奥司他韦对研究使用的50株不同型和亚型流感病毒皆有抑制病毒感染细胞的效果，IC50均〈25mg／L。药物对B亚型病毒的效果较差，IC50为19．97mg／L（15．16～22．36mg／L），高于A／H1N1亚型的8．15mg／L（0．02～22．36mg／L，P〈0．05）和A／H3N2亚型的10．92mg／L（0．08～19．72mg／L，P〉0．05）；对于不同年份分离的流感病毒，药物效果有所变化。结论磷酸奥司他韦对上海及周边地区的流感病毒具有较好的体外抗病毒效果，需要建立监测网络来监控药物的效果和病毒的耐药情况。

Objective To evaluate in vitro biological effect of oseltamivir carboxylate against various subtype influenza viruses isolated from Shanghai and its surrounding places during the 2004- 2006 influenza season, and then to determine the sensitivity and drug resistance of different strains to the compound. Methods Influenza viruses were isolated from cases of flu-like symptoms during influenza season in Shanghai, Wuxi and Deqing. Fifty isolates belonging to 3 subtypes were selected in this study. The anti-viral activity of oseltamivir carboxylate was determined by neutral-red uptake assay. The 50% inhibition concentration （IC50） served as the index of anti-viral effect. Results It was demonstrated that oseltamivir carboxylate could inhibit influenza virus effectively. IC50 in all isolates was lower than 25 mg/L. There were various IC50 ranges in different subtypes. Influenza B virus （Mean IC50 19.97 mg/L, 15.16-22.36 mg/L） appeared to be less sensitive than A/H1N1 （Mean IC50 8.15 mg/L, 0. 02-22. 36 mg/L, P 〈 0.05） or A/H3N2 （Mean IC50 10.92 mg/L, 0. 08-19. 72 mg/L, P 〈 0. 05）. Drug efficacies were varied in the viruses isolated from different influenza season. Conclusions Oseltamivir carboxylate can effectively inhibit influenza virus isolated from Shanghai and its surrounding places during the 2004- 2006 influenza seasons. Oseltamivir carboxylate resistance is not observed in this study. It is suggested that the Neuraminidase Inhibitor Susceptibility Network should be established to survey the susceptibility of influenza virus and the occurrence of drug resistance.